TY - JOUR
T1 - Structural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1
AU - Jojoa-Cruz, Sebastian
AU - Saotome, Kei
AU - Tsui, Che Chun Alex
AU - Lee, Wen Hsin
AU - Sansom, Mark S.P.
AU - Murthy, Swetha E.
AU - Patapoutian, Ardem
AU - Ward, Andrew B.
N1 - Funding Information:
We thank W. Anderson for managing the electron microscopy facility at Scripps Research, H. Turner for helping with data collection, and C. Bowman, L. Dong, and J.C. Ducom for assistance with computation. We acknowledge members of the Ward and Patapoutian labs for helpful advice. This work was supported by NIH grant R01 HL143297 and a Ray Thomas Edwards Foundation grant to A.B.W., and NIH grant R01 HL143297 to A.P. Work in M.S.P.S.’s lab is supported by Wellcome (grant 208361/Z/17/Z), BBSRC (grants BB/N000145/1 and BB/R00126X/1), and EPSRC (grant EP/R004722/1). K.S. was a postdoctoral fellow of the Jane Coffin Childs Memorial Fund for Medical Research. C.C.A.T. is supported by the Skaggs-Oxford Scholarship and the Croucher Foundation. A.P. is an investigator of the Howard Hughes Medical Institute. Molecular graphics and analyses performed with UCSF Chimera and UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and P41-GM103311, and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases.
Funding Information:
We thank W. Anderson for managing the electron microscopy facility at Scripps Research, H. Turner for helping with data collection, and C. Bowman, L. Dong, and J.C. Ducom for assistance with computation. We acknowledge members of the Ward and Patapoutian labs for helpful advice. This work was supported by NIH grant R01 HL143297 and a Ray Thomas Edwards Foundation grant to A.B.W., and NIH grant R01 HL143297 to A.P. Work in M.S.P.S.?s lab is supported by Wellcome (grant 208361/Z/17/Z), BBSRC (grants BB/N000145/1 and BB/R00126X/1), and EPSRC (grant EP/R004722/1). K.S. was a postdoctoral fellow of the Jane Coffin Childs Memorial Fund for Medical Research. C.C.A.T. is supported by the Skaggs-Oxford Scholarship and the Croucher Foundation. A.P. is an investigator of the Howard Hughes Medical Institute. Molecular graphics and analyses performed with UCSF Chimera and UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and P41-GM103311, and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Flycatcher1 (FLYC1), a MscS homolog, has recently been identified as a candidate mechanosensitive (MS) ion channel involved in Venus flytrap prey recognition. FLYC1 is a larger protein and its sequence diverges from previously studied MscS homologs, suggesting it has unique structural features that contribute to its function. Here, we characterize FLYC1 by cryo-electron microscopy, molecular dynamics simulations, and electrophysiology. Akin to bacterial MscS and plant MSL1 channels, we find that FLYC1 central core includes side portals in the cytoplasmic cage that regulate ion preference and conduction, by identifying critical residues that modulate channel conductance. Topologically unique cytoplasmic flanking regions can adopt ‘up’ or ‘down’ conformations, making the channel asymmetric. Disruption of an up conformation-specific interaction severely delays channel deactivation by 40-fold likely due to stabilization of the channel open state. Our results illustrate novel structural features and likely conformational transitions that regulate mechano-gating of FLYC1.
AB - Flycatcher1 (FLYC1), a MscS homolog, has recently been identified as a candidate mechanosensitive (MS) ion channel involved in Venus flytrap prey recognition. FLYC1 is a larger protein and its sequence diverges from previously studied MscS homologs, suggesting it has unique structural features that contribute to its function. Here, we characterize FLYC1 by cryo-electron microscopy, molecular dynamics simulations, and electrophysiology. Akin to bacterial MscS and plant MSL1 channels, we find that FLYC1 central core includes side portals in the cytoplasmic cage that regulate ion preference and conduction, by identifying critical residues that modulate channel conductance. Topologically unique cytoplasmic flanking regions can adopt ‘up’ or ‘down’ conformations, making the channel asymmetric. Disruption of an up conformation-specific interaction severely delays channel deactivation by 40-fold likely due to stabilization of the channel open state. Our results illustrate novel structural features and likely conformational transitions that regulate mechano-gating of FLYC1.
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UR - http://www.scopus.com/inward/citedby.url?scp=85124598796&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-28511-5
DO - 10.1038/s41467-022-28511-5
M3 - Article
C2 - 35165281
AN - SCOPUS:85124598796
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 850
ER -